Abstract/Project Summary Life-threatening bleeding occurs from many etiologies in children, such as intra and post-operative bleeding, gastrointestinal bleeding, disseminated intravascular coagulation, and traumatic injury. The epidemiology, therapies commonly used, and outcomes related to severe hemorrhage has not been systematically studied in children, and is a major gap in our knowledge in this high-risk population. Damage Control Resuscitation (DCR) principles have been developed to reduce death from hemorrhage in adult trauma patients. One important concept within DCR is called hemostatic resuscitation, which has been defined as a high ratio of plasma and platelets to RBCs (> 1:2 units), as well as a small plasma deficit (RBC total units - plasma total units), both starting very early in the resuscitation. To implement hemostatic resuscitation, Massive Transfusion protocols (MTP) have been developed in many adult and pediatric tertiary care centers. Despite a paucity of evidence supporting hemostatic resuscitation in children, it is being generalized to pediatric practice for both traumatic and non-traumatic etiologies. The MAssive Transfusion epidemiology and outcomes In Children (MATIC) study is a multicenter, prospective, observational study that will collect data on all MTP activations on children at participating centers. The goal of this study is to determine the epidemiology, therapies used, and outcomes for children requiring MTP activation from all etiologies. We will prospectively collect data on all MTP activations in a consecutive sample of approximately 502 patients from 35 academic pediatric tertiary care centers into a web-based database over a 22-month period. We will determine if patient specific factors and inter-hospital variability are associated with MTP practice and outcomes. Our primary hypothesis is that morbidity and mortality outcomes will vary by patient illness category (operative vs traumatic vs medical). We also aim to determine if early and sustained hemostatic resuscitation is associated with increased survival in children with traumatic injury requiring MTP activation. We have collected preliminary data indicating the feasibility of the study and validity of the data collection methods. We have also limited the analysis of hemostatic resuscitation on outcomes to children with traumatic injury to reduce heterogeneity in the study population. This study is innovative due to the absence of pediatric multicenter data published on the epidemiology, therapies, and outcomes for children in this population. Our statistical analysis is also innovative. We will develop a sophisticated model that will incorporate propensity scores with the timing, ratio, and deficits of plasma and platelets to RBCs to determine if ?hemostatic resuscitation? is associated with improved outcomes. Completion of this study will provide preliminary data that will provide support for large comparative effectiveness studies to determine which DCR principles affect outcomes in children with or without traumatic injury with severe life-threatening bleeding. High quality trials are essential to improve clinical practice since the mortality in this population ranges from 35 to 78%.